Studies concerning immunity in children with short bowel syndrome are sparse and refer only to selected immunological aspects. Realizing the crucial role of GALT for development of mucosal and systemic immunity, massive bowel resection could potentially result in serious immune dysfunction. Factors that may contribute to immune disturbances in SBS include: reduction of bowel surface for GALT development, lack of normal food antigen processing, bacterial overgrowth, increased permeability, bacterial translocation and influence of TPN on systemic immunity .
Some publications dealing with immunological consequences of short bowel syndrome in children have been revised by Duran, but none of them investigated mechanism of systemic adaptive immune response . Moreover, all the analyzed publications concerned patients receiving parenteral nutrition and none of the studies related to late immune consequences of bowel resection. The only existing study describing lymphocytes population in short bowel syndrome refers to adults. It documents that 10 SBS patients presented with normal values of CD3+, CD4+, CD8 + lymphocytes, but reduced B lymphocytes in comparison to healthy individuals . One has to note, however, that bowel resection in adulthood is a completely distinct state, as the removal of intestine takes place in the individuals in whom immunity had previously undergone physiological development. In our cohort no differences in absolute counts of lymphocytes T, including CD4 +, CD8 + cells and also B lymphocytes were found. Only the proportions of lymphocytes T, B and CD8 + in the studied group significantly differed from the control group, showing reduction in B lymphocytes frequency and increased rates of CD8 + and T lymphocytes.
We have also noted normal rate and number of activated T lymphocytes in SBS patients. This group of lymphocytes was particularly interesting, as T cell activation being the crucial process of development of adaptive immune response takes place mainly in mucosal associated lymphoid tissue including GALT. We have documented significantly lower absolute count and proportion of NK cells in SBS group comparing to healthy controls. This population of cells was not investigated by the authors of the quoted publication. The decrease in NK cells has been observed in some congenital and acquired conditions, mostly autoimmune diseases, but has never been reported in SBS [9, 10]. We have to note that, although significantly lower, NK numbers were within the normal range in all our patients, thus cannot be considered as a sign of immunodeficiency. This preliminary observation needs to be confirmed in a larger cohort. Moreover, all the subjects displayed normal levels of immunoglobulins, what is an additional argument supporting our observation that immunodeficiency is not a late effect of bowel resection. Furthermore none of our patients demonstrated clinical signs of impaired immunity according to criteria established by ESID . Although 4 patients had undergone catheter-related sepsis during TPN, no other severe infections were observed in the studied group. Likewise the quoted publication, our study was retrospective assessment of peripheral lymphocytes at different time after surgery, meaning that the studied group was not homogenous. The shortest time after resection in our cohort was 8 months, while the longest amounted to 10 years. It is worth noting that even the youngest subject in the studied group presented with the normal values of the studied subpopulations, what may indicate that although reduced, the remaining bowel surface is sufficient for the lymphocytes T and B to populate bowel and get activated. It has not however been clarified how long the reconstruction of GALT lasts. Probably some transient immunological imbalance appears after bowel resection, as it has been demonstrated in experimental studies. Barrena et al reported systemic immune alterations, such as reduction in CD4 + lymphocytes and B lymphocytes, in SBS animal model 7 days after surgery . It may however reflect surgical stress rather than immunological imbalance caused by bowel removal, especially that analogical disturbances were also observed after other surgical interventions . Another study demonstrated changes in circulating lymphocytes numbers also 3 weeks after surgery . Short duration of the mentioned studies does not allow to conclude whether the presented abnormalities persist or rather they tend to evolve into full immune reconstruction in experimental animals. Therefore, future prospective studies are needed to clarify evolution of immune alterations following bowel resection in animals and in humans, especially children in whom intestinal loss takes place in newborn period.
We also examined relationships between lymphocytes subpopulations and the length of resected bowel. Statistically significant inverse correlation was noted only for the rate of CD4 + cells. It could be explained by the reduction of the surface for antigen stimulation, which is necessary for maturation and proliferation of CD4 + cells . We do not consider this finding relevant, as it referred only to the rate, but not an absolute number of CD4 + and may result from small sample size. Analysis of the relations between the studied subpopulations and the time after surgery revealed more findings. Surprisingly we found negative correlations for the absolute numbers of: lymphocytes, lymphocytes B, T, CD4 + and percentages of lymphocytes CD4 + and activated T cells. We would rather expect an increase of these amounts over time as a sign of immune reconstruction and maturation. It should be noted that in our subjects operated in the first days of life, the time since resection exactly corresponds to the child’s age. Therefore we also evaluated the correlation between the lymphocyte subpopulations and the age of children in control group, but we noted no statistically significant results. Thus, it can be speculated that, if this trend is sustained, the patients might develop immune deficits in future, which points out to the need for longer follow up in SBS patients.
In conclusion, our results suggest that children with short bowel present neither with clinical signs of immunodeficiency, nor with deficits in peripheral lymphocyte populations and serum immunoglobulins. Decreased number of NK cells in SBS patients compared to healthy controls needs to be verified in larger cohort. The tendency of the lymphocyte subpopulations to decrease over time after resection indicates the necessity for longer follow- up, since it can be speculated that SBS patients might develop immune deficits in future. Further research concerning other parameters of adoptive immunity in children with short bowel syndrome is warranted.